Cleaning and disinfection of surgical and medical instruments and appliances

ABSTRACT

The invention relates to the use of a cleaning agent that contains surfactants and has a pH value of at least 11 when diluted in an aqueous solution and ready for use. Said cleaning agent is used to destabilize prions during mechanical and manual cleaning and/or disinfection of medical and/or surgical instruments and appliances. It has been recognized that this combination enables a reliable destabilization of prions during the mechanical reconditioning of surgical instruments.

This application is a §371 US National Entry of InternationalApplication No. PCT/EP03/00849 filed Jan. 28, 2003, hereby incorporatedherein by reference, which claims priority to German Patent ApplicationSer. No. 102 03 225.4, filed Jan. 28, 2002.

FIELD OF THE INVENTION

The invention relates to the field of cleaning and disinfection ofmedical and/or surgical instruments and apparatuses.

BACKGROUND OF THE INVENTION

Creutzfeldt-Jakob Disease (CJD), according to current knowledge, is anencephalopathy caused by prions. Prions are infectious protein particleswhich cannot be readily destabilized by conventional substancesattacking nucleic acid and have high stability toward chemical andphysical influences. Cleaning and disinfection of medical or surgicalinstruments and apparatuses which are possibly contaminated with prionsis therefore problematic. In the literature (Bundesgesundheitsblatt July1998, 279-298), it is proposed to decontaminate instruments contaminatedwith CJD material using 1 to 2 M NaOH for a period of 24 h, or by steamsterilization for a period of 1 h at 134° C. Alternatively,decontamination using the highly toxic guanidinium thiocyanate isproposed. These decontamination processes are extremely complex andcannot be carried out in the routine preparation of instruments.

SUMMARY OF THE INVENTION

The object underlying the invention is to provide a possible method forthe cleaning or disinfection of medical or surgical instruments andapparatuses, in which prions are destabilized with sufficientreliability, preferably are also inactivated. The invention is to besuitable for routine use, in particular in mechanical instrumentcleaning and preparation and is not to require any complex separatedecontamination, as in the prior art.

The invention therefore relates to the use of a cleaning compositionwhich comprises surfactants and has a pH of at least 11 when diluted inaqueous solution in ready-to-use form, for destabilizing and/orinactivating prions in the mechanical or manual cleaning and/ordisinfection of medical and/or surgical instruments and apparatuses.

First some terms used in the context of the invention are to beexplained.

DEFINITIONS

The term cleaning composition denotes any ready-to-use formulation whichis used either directly or diluted with water for the cleaning ordisinfection of the corresponding instruments. In the context of theinvention, the term cleaning composition includes the term disinfectant.The cleaning composition can be formulated in solid form or preferablyin liquid form. As cleaning solution, that is to say diluted in aqueoussolution in ready-to-use form, the cleaning composition has a pH of 11or above.

The cleaning composition used according to the invention comprisessurfactants. This denotes compounds which lower the surface tension,that is to say amphiphilic compounds having at least one hydrophobicmoiety and one hydrophilic moiety. In the context of the invention, itis possible to use all surfactants, for example anionic surfactants,nonionic surfactants, cationic surfactants, amphoteric surfactants andblock copolymers (in particular made from ethylene oxide and propyleneoxide units). By way of example, reference is made to RömppChemielexikon [Römpp's Chemistry Lexikon], 10th edition, headword“surfactants”.

The invention is used in the mechanical and manual cleaning and/ordisinfection of medical and/or surgical instruments and/or apparatuses.“Mechanical” means that the process preferably proceeds automatically ina dishwashing machine and no human intervention is necessary in thecourse of cleaning or disinfection. In particular, according to theinvention, a conventional dishwashing and preparation machine forsurgical instruments can be employed. Particularly preferably, theinvention is used in mechanical cleaning and disinfection. It can beused, in particular, for routine daily instrument cleaning.

The terms “cleaning and/or disinfection” cover the steps required in thetreatment of used instruments and apparatuses up to the preferablysterile state in which they can be reused.

Medical and/or surgical instruments and apparatuses are all appliancesused in the medical and hospital sector and parts thereof which are inprinciple accessible to mechanical cleaning and disinfection.

Destabilizing prions means that infectious prion material possiblyadhering to the instrument surface is at least partially destabilized.In a destabilization, the pathogenic conformation of the prion moleculeis no longer present.

Prion inactivation has occurred if, in an animal test, it is establishedthat the infectivity of a prion-containing brain extract is no longerpresent after a treatment with a composition or process under test.

DESCRIPTION OF THE INVENTION

It is known that prions are embedded in fatty tissue and are themselveshydrophobic and are thus accessible with difficulty to water and aqueoussolutions.

The invention is based on the surprising finding that prions may bedestabilized relatively simply in a strongly alkaline environment, if asurfactant is simultaneously present, in the context of routine, inparticular mechanical, instrument cleaning and preparation. The exactmechanism of action of the inventive combination has not been studied,but it is assumed to start from the fact that surfactants loosen thetertiary structure of the prions and thus facilitate theirdestabilization in the alkaline environment. The pH of the cleaningsolution diluted in ready-to-use form is preferably at least 11, furtherpreferably at least 11.5, further preferably at least 12, furtherpreferably at least 12.5. The cleaning composition preferably comprisesalkali metal hydroxides such as sodium hydroxide or preferably potassiumhydroxide. The use of potassium hydroxide facilitates the provision of acleaning composition in the form of a concentrate, since potassiumhydroxide solutions, at low temperatures, have a lesser tendency tocrystallize out than sodium hydroxide solutions. The cleaningcomposition can additionally comprise alkanolamines.

The addition of surfactants to the highly alkaline cleaning solution canmarkedly reduce the surface tension and interfacial tension. It isthought that the prions are thereby made more accessible to the alkalineactive ingredient and at least the tertiary structure of the prions canbe destroyed and the prions can be destabilized or inactivated.

In principle, nonionic surfactants, for example fatty alcohols, are mostsuitable for reducing the surface tension of an aqueous solution. Theyhave the additional advantage that they foam less and thus prevent orreduce the unwanted foam formation in the cleaning of medicalinstruments. Foam formation can impair in particular the cleaning of forexample narrow-bore tubes of endoscopes or the like. Nonionicsurfactants, however, in a strongly alkaline environment, are oftendifficult to bring into solution. It is therefore preferred in thecontext of the invention to combine the nonionic surfactant withcationic, anionic or particularly preferably amphoteric surfactantswhich can act as solubilizer for the nonionic surfactant.

The cleaning solution diluted in ready-to-use form preferably has asurface tension of less than 50 mN/m, preferably less than 40 mN/m,further preferably less than 35 mN/m, further preferably less than 30mN/m. The surface tension is determined by the plate-ring method asspecified in DIN 53993.

A further aspect of the invention is avoiding or reducing theredeposition of prion-containing contaminants on the instruments. Theterm redeposition denotes the redeposition of a contaminant alreadyremoved from a contaminated surface onto another, possibly previouslyuncontaminated, surface of the instrument to be cleaned. Redeposition isa particular problem with the decontamination, by 24-hour immersion in 1to 2 M NaOH, recommended in the Bundesgesundheitsblatt (July 1998,279-298).

The use of surfactants, provided in the context of the invention,already prevents redeposition, since the surfactants can emulsifydetached prion constituents and thus keep them in suspension in theaqueous solution. Particularly preferably, in the context of theinvention, to avoid or decrease redeposition, the cleaning compositionadditionally comprises hardness dispersants. Hardness dispersants whichcan be used are, for example, phosphates and polyphosphates, complexingagents or chelating agents, or other builders. Hardness dispersantssupport the emulsifying action of the surfactants and thus contribute tothe prevention of redeposition.

An important aspect of the invention is its suitability for routine, inparticular mechanical, instrument cleaning and preparation. For suchroutine cleaning, in the prior art, customarily weakly acidic or weaklyalkaline (for example enzymatic) cleaners are used, since stronglyalkaline solutions can lead to increased loading or corrosion and thuswear of various materials and surfaces which are used in medicalinstruments and apparatuses. Problems from this point of view are, forexample, silicone elastomers, chrome-plated instruments, solderedcompounds of silver and tin, adhesive bonds and sealing materials,plastic coatings, for example color codings, glass fiber lightconductors and optical surfaces having an antireflection coating.Particular problems are aluminum surfaces, in particular anodizedaluminum surfaces, since alkaline solutions exhibit particularaggression toward these. Said problems occur, for example, particularlyin the cleaning of endoscopes and constituents thereof, since here thesurfaces to be cleaned have a great variety of materials.

In a particularly preferred embodiment of the invention, the cleaningcomposition therefore additionally comprises corrosion inhibitors. Thiscovers any substance which, in the alkaline solution, inhibits itsattack on surfaces, in particular having metallic surfaces such asaluminum or anodized aluminum. Suitable inhibitors are, for example,polymeric silicates, for example waterglass, phosphoric acid esters, orthe like. Suitable phosphoric acid esters are mono- and/or diesters ofphosphoric acid with aliphatic alcohols of chain length C₁ to C₂₂ and/oraliphatic diols and/or aliphatic polyols of chain length C₂ to C₂₂.Particular preference is given to a diester of phosphoric acid withbutanol on one side and ethylene glycol on the other. This ester iscommercially available under the name Hordaphos® MDGB. According to theinvention, despite the use of highly alkaline cleaning solutions, a mildaction on, for example, anodized aluminum surfaces is achieved in thismanner.

According to the invention, from the constituents of the cleaningcomposition, preferably a liquid concentrate is formulated which can bediluted with water to give the ready-to-use cleaning solution. In thisconcentrate, the alkali content (calculated as KOH) is preferablybetween 2 and 30% by weight, further preferably 35% by weight, furtherpreferably 10 and 30% by weight, further preferably 15 and 25% byweight. The surfactant content is preferably between 2 and 25% byweight, further preferably 2 and 15% by weight, further preferably 5 and15% by weight, further preferably 5 and 10% by weight. This concentrateis preferably made up at concentrations of 0.5 to 5, preferably 0.5 to2, particularly preferably 0.5 to 1.5, percent by volume with water togive a ready-to-use solution.

As mentioned above, the concentrate can comprise at least one complexingagent, in particular chelating agent. The complexing agents serve tosoften water and can enhance the cleaning action compared with limesoaps by complexing alkaline earth metal ions. The complexing agents canbe homo-, co- or terpolymers based on acrylic acid or alkali metal saltsthereof, in addition phosphonic acids or alkali metal salts thereof, forexample 1-hydroxyethane-1,1-diphosphonic acid,aminotrismethylenephosphonic acid,ethylenediaminotetrakismethylenephosphonic acid,phosphonobutanetricarboxylic acid, tartaric acid, citric acid andgluconic acid; in addition nitrilotriacetic acid orethylenediaminetetraacetic acid or salts thereof.

The concentrate can comprise nitrilotriacetic acid and/or a salt of thisacid, particularly preferably its trisodium salt. The addition of NTA isadvantageous if the concentrate is to be made up with water having highmineral contents (hard water) to give a ready-to-use solution.

To the concentrate, there can be added customary preservatives, forexample p-hydroxybenzoic acid or methyl esters thereof,5-bromo-5-nitro-1,3-dioxane, salicylic acid,2-naphthyl-m-N-dimethylthiocarbanilate,5-chloro-5-methyl-4-isothiazolin-3-one, 2-methyl-4-isothiazolin-3-oneand also mixtures of the two last-mentioned compounds. A preferredpreservative is p-hydroxybenzoic acid or methyl esters thereof. Usingthese preservatives avoids microbial and fungal infestation of thecleaning composition concentrate.

If required, formulation aids (solubilizers) can be added, for examplesodium cumenesulfonate, sodium toluene-sulfonate, sodiumxylenesulfonate, urea, glycols, in particular polypropylene glycols andpolyethylene glycols, methylacetamide and fatty alcohols, for examplecetyl alcohol.

The enumeration of possible constituents is not limiting. In addition,it is possible to add, for example, wetting agents, emulsifiers,antifoam agents or the like. It is advantageous, for example, to addN-acyl glutamate as wetting agent.

The time of action of the cleaning composition is according to theinvention preferably 1 to 60 min, further preferably 1 to 30 min,further preferably 5 to 30 min, further preferably 10 to 20 min. Beforeand/or after the action of the inventively used cleaning composition,further preliminary cleaning, cleaning, rinsing or final rinsing ordisinfection steps can be provided. It is preferred first to carry out apreliminary rinse to remove coarse contaminants, then to perform aninventive cleaning/disinfection, followed by a rinse with hot water (93°C.) for thermal disinfection and removal of cleaning compositionresidues.

The cleaning is carried out according to the invention, preferably at atemperature from room temperature to 93° C., further preferably from 40to 93° C., further preferably from 50 to 80° C., particularly preferablyfrom 50 to 60° C. Likewise preference is given to a temperature rangefrom room temperature (18° C.) to 50° C. or from room temperature to 40°C.

In the case of mechanical cleaning, particular preference is given totemperatures from 50 to 60° C., in particular about 50° C., and a timeof action of 10 to 20 min, preferably about 10 min. In the case ofmanual cleaning by immersion in a cleaning solution, preference is givento a time of action of about 10 min at room temperature. In the case ofmanual cleaning, preferably a higher concentration, preferably aconcentration of the cleaner which is twice as high as in the mechanicalcleaning, is used. For example, the cleaner concentrate according to theexample 1 below is used in the context of mechanical cleaning preferablyin a use concentration of about 0.5% by volume, in manual cleaning at aconcentration of 1% by volume.

Illustrative examples of the invention are described hereinafter on thebasis of the illustration and the examples.

DESCRIPTION OF THE DRAWINGS

The illustration shows anodized aluminum plates before and aftertreatment with two different highly alkaline cleaners.

EXPERIMENTAL EXAMPLES Example 1

A cleaning composition concentrate is prepared according to the tablebelow. The amounts of the starting materials to be used are given inparts by weight.

Potassium tripolyphosphate, 50% 42.78 Potassium hydroxide, 45% 22.32Sodium alkylaminodipropionate 6.00 Bardac LF¹ 0.50 Fatty alcohol,C10/12, 4EO, 0.50 4–5 PO² Sodium waterglass 27.90 ¹Cationic surfactant(dioctyldimethylammonium chloride) ²Block copolymer of C10/C12 fattyalcohols having 4 ethylene oxide units and 4–5 propylene oxide units.

Example 2

In a one-tank washing machine for medical and surgical instruments, theinstruments which are to be cleaned and which are suspected to have acontamination with prions are first pre-rinsed with cold water. Thewashing machine is then filled with cold water and the cleaningcomposition concentrate according to example 1 is added at aconcentration of 0.5% by volume. The cleaning solution is heated to 55°C. and circulated for 10 min at this temperature with spraying of theinstruments. Rinsing is then performed with cold deionized water.Finally a thermal disinfection with deionized water is performed at 93°C. This thermal disinfection is simultaneously the final rinse.

Example 3

The surface tension was determined as specified in DIN 53993 for thefollowing liquids:

dionized water 73 mN/m 0.1 N NaOH in deionized water 72 mN/m 1% byvolume cleaner solution according 33 mN/m to example 1 in Hamburg citywater

It is seen that the cleaning solution from a concentrate according toexample 1 has a markedly decreased surface tension compared with asimply alkaline solution. This solution comprises the fatty alcohol asnonionic surfactant and also sodium alkylaminodipropionate assolubilizing amphoteric surfactant.

Example 4

Roughened microscope slides are dirtied with 50 mg of a blood-egg yolkmixture, dried at 55° C. for 2 h and then immersed in a stirred bath for10 min at room temperature. The medium used for the immersion bath isdeionized water, 0.1 N NaOH or a 1% strength by volume cleaning solutionof the cleaning composition concentrate according to example 1. Theresidual amount of fouling then determined is 20% by weight for water,35% by weight for 0.1 N NaOH and less than 5% by weight for the cleaner,as immersion bath medium used.

Example 5

To test the care of material of anodized aluminum surfaces, anodizedaluminum plates are exposed to a cleaning medium in the Miele G7736dishwashing machine for 10 min at 55° C. Both new colorless and alsoblue anodized aluminum plates are used. The cleaning medium is 0.1 MNaOH having a pH of 12.7 and a 1% strength by volume cleaning solutionof the cleaning composition concentrate according to example 1. Theplates are then inspected visually. The results shown in theillustration shows that in the plates treated with NaOH, the anodizedlayer is markedly eroded. In contrast thereto, the plates treated withthe cleaner have no visible damage to the anodized layer.

1. A method of routine cleaning of and prion destabilization on reusablemedical and/or surgical instruments and apparatuses after use and priorto reuse, comprising: a) providing: i) a surface of a reusable medicalor surgical instrument or apparatus contaminated with a prion; and ii) acomposition comprising surfactants and KOH, wherein said composition hasa pH of at least 11.5 when diluted in an aqueous solution inready-to-use form, for destabilizing prions in the routine mechanical ormanual cleaning and/or disinfection of said reusable medical or surgicalinstrument or apparatus prior to reuse; and b) treating said surface ofsaid reusable medical or surgical instrument or apparatus with saidcomposition, wherein the time of action of the cleaning composition is 5to 30 min, wherein said treatment causes the destabilization of prionson said surface of said reusable medical or surgical instrument orapparatus, and wherein said treating has less corrosive effect on thematerial of said surface than treatment of the material of said surfacewith NaOH at a concentration of 1 N or greater.
 2. The method of claim1, wherein said composition has a pH of at least
 12. 3. The method ofclaim 2, wherein said composition has a pH of at least 12.5.
 4. Themethod of claim 1, wherein said composition further comprisesalkanolamines.
 5. The method of claim 1, wherein said surfactantscomprise nonionic surfactants.
 6. The method of claim 1, wherein saidcomposition has a surface tension of less than 50 mN/m.
 7. The method ofclaim 1, wherein said composition has a surface tension of less than 40mN/m.
 8. The method of claim 1, wherein said composition has a surfacetension of less than 35 mN/m.
 9. The method of claim 1, wherein saidcomposition has a surface tension of less than 30 mN/m.
 10. The methodof claim 1, wherein said composition comprises hardness dispersants. 11.The method of claim 1, wherein said composition comprises one or more ofphosphates or polyphosphates.
 12. The method of claim 1, wherein saidcomposition comprises one or more corrosion inhibitors.
 13. The methodof claim 12, wherein said one or more corrosion inhibitors are selectedfrom the group consisting of polymeric silicates and phosphoric acidesters.
 14. The method of claim 1, wherein said treating is for a timeperiod of 10 to 20 minutes.
 15. The method of claim 1, wherein saidtreating is performed at temperature from room temperature to 93° C. 16.The method of claim 1, wherein said treating is performed at temperatureof from room temperature to 93° C.
 17. The method of claim 1, whereinsaid treating is performed at temperature of from 40 to 93° C.
 18. Themethod of claim 1, wherein said treating is performed at temperature offrom 50 to 60° C.